In vivo eye surface residence determination by high-resolution scintigraphy of a novel ion-sensitive hydrogel based on gellan gum and kappa-carrageenan

• Published in: European journal of pharmaceutics and biopharmaceutics 2017-05, Vol.114, p.317-323
• Main Authors: Fernández-Ferreiro, Anxo, Silva-Rodríguez, Jesús, Otero-Espinar, Francisco Javier, González-Barcia, Miguel, Lamas, María Jesús, Ruibal, Alvaro, Luaces-Rodríguez, Andrea, Vieites-Prado, Alba, Lema, Isabel, Herranz, Michel, Gómez-Lado, Noemí, Blanco-Mendez, José, Gil-Martínez, María, Pardo, María, Moscoso, Alexis, Cortes, Julia, Sánchez-Martínez, María, Pardo-Montero, Juan, Aguiar, Pablo
• Format: Article
• Language: English
• Subjects: 99mTc-DTPA; Animals; Carrageenan - adverse effects; Carrageenan - chemistry; Cell cytotoxicity; Cornea - diagnostic imaging; Cornea - metabolism; Drug Compounding; Excipients - chemistry; Het Cam; Hydrogels - adverse effects; Hydrogels - chemistry; Ion sensitive hydrogel; Irritants; Isotope Labeling; Male; Ocular pharmacokinetics; Ophthalmic formulations; Ophthalmic Solutions; Polysaccharides, Bacterial - adverse effects; Polysaccharides, Bacterial - chemistry; Radionuclide Imaging; Radiopharmaceuticals - chemistry; Radiotracers; Rats; Rats, Sprague-Dawley; Scintigraphy
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2017.01.023

[Display omitted] In last years, sensitive hydrogels have become a breakthrough in ophthalmic pharmaceutical technology aimed at developing new strategies to increase the residence time of active substances. In a previous paper, we qualitatively demonstrated the capacity of a new ion sensitive hydrogel to increase the residence time. Nevertheless, the clearance of the gel from the ocular surface was not quantifiable with the used methodology. The aim of the present work was to use a well-established approach based on scintigraphy to quantitatively estimate the residence time of the previously proposed hydrogel. The rat corneal residence time of a topic ophthalmic formulation containing gellan gum and kappa carragenan (0.82% w/v) labeled with 99mTc-DTPA radiotracer was evaluated and compared with the residence of an aqueous solution. Ophthalmic safety studies such as eye irritation or passage through the cornea were also carried out. After 1.5h of contact, 77% of the hydrogel remained in the ocular surface, presenting kinetics of disappearance one-phase decay and a half time of 262min. We conclude that the novel ophthalmic hydrogel developed with kappa carrageenan and gellan gum remains for long periods of time on the corneal surface, presenting a drop that fits an exponential decay.